Atherosclerosis development in SLE patients is not determined by monocytes ability to bind/endocytose Ox-LDL

Abstract

Patients with systemic lupus erythematosus (SLE) have a high risk of developing cardiovascular disease; however, the mechanisms involved in the early onset of atherosclerosis in these patients are not clear. Scavenger receptors, CD36 and CD163 are expressed by mononuclear phagocytes and participate in the binding and uptake of oxidized low-density lipoproteins (Ox-LDL), contributing to foam-cells formation and atherosclerosis development. The aim of the present study was to evaluate CD36⁺ and CD163⁺ expression and Ox-LDL removal by monocytes from SLE and atherosclerotic patients, compared to similar age-range healthy controls. Healthy controls, SLE, and atherosclerotic patients were evaluated for carotid intima media thickness (CIMT), lipid profile, and native LDL (N-LDL) and Ox-LDL binding/endocytosis. SLE patients presented decreased high-density lipoproteins (HDL) and increased Triglyceride levels, and half of the SLE patients had increased CIMT, compared to their healthy controls (HC_SLE). The number of CD14⁺CD163⁺ cells was increased in atherosclerosis healthy controls (HC_Atheros) compared to HC_SLE, but there were no differences between SLE or atherosclerotic patients and their respective healthy controls. Clearance assays revealed a similar capacity to bind/endocytose Ox-LDL by monocytes from SLE patients and HC_SLE, and an increased binding and endocytosis of Ox-LDL by monocytes from atherosclerotic patients, compared to HC_Atheros. The decreased CD36 and CD163 expression observed in atherosclerotic and SLE patients, respectively, suggest that these inflammatory conditions modulate these receptors differentially. The increased CIMT observed in SLE patients cannot be explained by Ox-LDL binding/endocytosis, which was comparable to their controls.

Keywords::

• Atherosclerosis
• SLE
• scavenger receptors
• OxLDL
• endocytosis

Acknowledgements

Thanks to the Hospital San Vicente de Paul for allowing the development of the project, to the Flow Cytometry Unit at the SIU (Sede de Investigación Universitaria), Universidad de Antioquia, and to Libia M. Rodríguez for her helpful input concerning the statistical analysis. The authors also thank the patients and the healthy volunteers.

Declaration of interest: This work was supported by Colciencias, Grant 11150416348 and “Proyecto de Sostenibilidad”, Universidad de Antioquia. LMY was beneficiary of a doctoral fellowship from Colciencias and received partial funding from “Proyecto de Sostenibilidad” Universidad de Antioquia. Authors' salaries were paid either by Colciencias (LMY, JL and GM), the Universidad de Antioquia (MR, LAR, LFG and GV) or by Universidad Central de Venezuela (JBS). None of the authors has any potential financial conflict of interest related to this manuscript. The authors alone are responsible for the content and writing of the paper.